Evaluation of cytotoxic and tyrosinase inhibitory activities of 2-phenoxy(Thiomethyl) pyridotriazolopyrimidines: In vitro and molecular docking studies

• Published in: Anti-Cancer Agents in Medicinal Chemistry
• Main Author: Abuelizz H.A.; Anouar E.H.; Marzouk M.; Hasan M.H.; Saleh S.R.; Ahudhaif A.; Alburikan K.A.; Al-Salahi R.
• Format: Article
• Language: English
• Published: Bentham Science Publishers 2020
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85089626979&doi=10.2174%2f1871520620666200627212128&partnerID=40&md5=e2edf0d0a7fbf7e8e6162f29ddf9b704

Background: The use of tyrosinase has confirmed to be the best means of recognizing safe, effective, and potent tyrosinase inhibitors for whitening skin. Twenty-four 2-phenoxy(thiomethyl)pyridotriazolopyrimidines were synthesized and characterized in our previous studies. Objective: The present work aimed to evaluate their cytotoxicity against HepG2 (hepatocellular carcinoma), A549 (pulmonary adenocarcinoma), MCF-7 (breast adenocarcinoma) and WRL 68 (embryonic liver) cell lines. Methods: MTT assay was employed to investigate the cytotoxicity, and a tyrosinase inhibitor screening kit was used to evaluate the Tyrosinase (TYR) inhibitory activity of the targets. Results: The tested compounds exhibited no considerable cytotoxicity, and nine of them were selected for a tyrosinase inhibitory test. Compounds 2b, 2m, and 5a showed good inhibitory percentages against TYR compared to that of kojic acid (reference substance). Molecular docking was performed to rationalize the Structure-Activity Relationship (SAR) of the target pyridotriazolopyrimidines and analyze the binding between the docked-selected compounds and the amino acid residues in the active site of tyrosinase. Conclusion: The target pyridotriazolopyrimidines were identified as a new class of tyrosinase inhibitors. © 2020 Bentham Science Publishers.